Synthesis of 2′-Deoxy-2′-[18F]Fluoro-9-β-D-Arabinofuranosylguanine: a Novel Agent for Imaging T-Cell Activation with PET

Abstract

For the first time to the best of our knowledge, [(18)F]F-AraG has been successfully synthesized by direct fluorination of an appropriate precursor of a guanosine nucleoside. This approach maybe also useful for the synthesis of other important positron emission tomography (PET) probes such as [(18)F]FEAU, [(18)F]FMAU, and [(18)F]FBAU which are currently synthesized by multiple steps and involve lengthy purification. The cell uptake studies support future studies to investigate the use of [(18)F]F-AraG as a PET imaging agent of T cells.

Multiplexed imaging for diagnosis and therapy

“…For instance, PET generally informs on tissue phenotypes or processes (such as receptor expression [11][12][13][14][15][16] , microenvironment 17,18 , metabolism 16,[19][20][21][22][23] or perfusion) with outstanding sensitivity, but it is hampered by low resolution, scarcity of anatomic detail and dosimetric stipulations 24 . In contrast, MR provides anatomic detail with exquisite resolution, but lacks the sensitivity offered by radionuclide imaging; specific aspects of individual modalities are indicated in Table 3 (refs 24-31 ).…”

“…The resulting Cerenkov Radiation (CR) is detectable with charge-coupled device (CCD) cameras, and the data acquired by PET and Cerenkov luminescence imaging (CLI) are largely in agreement, when light tissue penetration is taken into account. The resolution and sensitivity of CLI are inversely related, as both are dependent on the distance a beta-particle travels while above the energetic threshold for Cerenkov emission (they are thus radioisotope-dependent; for 18 F this distance is ~0.3mm). Also, the sensitivity is a function of the refractive index of the tissue.…”

“…In patients with diverse cancer types, FDG and 18 F-NaF can be combined in a single PET-CT scan by administering the two radiopharmaceuticals simultaneously or in sequence on the same day 153 . Positive attributes to the use of the two tracers in multiplexing are improved workflow and patient convenience, the reduced radiation exposure from the CT component, and the enhanced sensitivity for the detection of osseous lesions compared to either 18 F-FDG or 18 F-NaF alone. Other studies combining these two agents 114,154 led to similar conclusions; this is also in line with the outcome of the combination of FDG with 11 C-acetate in metastatic liver cancer 155 .…”

“…Recently, FDG-PET CT was formally incorporated into standard staging for FDGavid lymphomas as part of the Lugano classification 156 , where a bone-marrow biopsy is no longer indicated for the routine staging of Hodgkin lymphoma and of most diffuse large B-cell lymphomas. The FDA has approved 11 C-choline and 18 F-fluciclovine for use in staging recurrent prostate cancer, and 68 Ga-DOTATATE for staging neuroendocrine cancer. In all cases opportunities exist for improving accuracy or for reducing the need of further imaging through multiplexing, so as to extend indications of imaging in the patient population.…”

“…Multiplexed molecular imaging instead provides a comprehensive, noninvasive view of tumour pathology and anatomy, and enables the rational selection of therapy, as well as insight into the optimal dosage, early-response assessment and subsequent treatment planning 143,208,[218][219][220] . For example, multiplexed PET in the early-response assessment of mice to VEGF 121 /rGel therapy in a breast-cancer model 220 Ga-DOTA-peptide, and the development of cyclotron-generated 18 F-analogues (e.g., FET-AG-TOCA) for wide patient coverage, underscores the potential role of PET in therapy selection and in the evaluation of potential responses to somatostatin-receptortargeted chemotherapies [221][222][223][224][225] (Fig. 3b).…”